Ma D W L, Arendt B M, Hillyer L M, Fung S K, McGilvray I, Guindi M, Allard J P
Department of Human Health and Nutritional Sciences, College of Biological Science, University of Guelph, Guelph, Ontario, Canada.
Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Nutr Diabetes. 2016 Jul 18;6(7):e220. doi: 10.1038/nutd.2016.27.
There is growing evidence that nonalcoholic fatty liver disease (NAFLD) is associated with perturbations in liver lipid metabolism. Liver phospholipid and fatty acid composition have been shown to be altered in NAFLD. However, detailed profiles of circulating lipids in the pathogenesis of NAFLD are lacking.
Therefore, the objective of the present study was to examine circulating lipids and potential mechanisms related to hepatic gene expression between liver biopsy-proven simple steatosis (SS), nonalcoholic steatohepatitis (NASH) and healthy subjects.
Plasma phospholipid and fatty acid composition were determined in 31 healthy living liver donors as healthy controls (HC), 26 patients with simple hepatic steatosis (SS) and 20 with progressive NASH. Hepatic gene expression was analyzed by Illumina microarray in a subset of 22 HC, 16 SS and 14 NASH.
Concentrations of phosphatidylethanolamine (PE) increased relative to disease progression, HC<SS<NASH (170<210<250 μg ml(-1)), and was significantly different (P<0.05) between HC and NASH. Circulating phosphatidylserine (PS) and phosphatidylinositol were higher in SS and NASH compared with HC (P<0.05), but there was no difference between SS and NASH. Fatty acid composition of phospholipids was also remodeled. In particular, docosahexaenoic and arachidonic acid were higher (P<0.05) in SS and NASH relative to HC in PS. Differentially expressed hepatic genes included ETNK1 and PLSCR1 that are involved in PE synthesis and PS transport, respectively.
The present study demonstrates that there is a disruption in phospholipid metabolism that is present in SS, but more pronounced in NASH. Intervention studies targeted at lipid metabolism could benefit SS and NASH.
越来越多的证据表明，非酒精性脂肪性肝病（NAFLD）与肝脏脂质代谢紊乱有关。NAFLD患者的肝脏磷脂和脂肪酸组成已被证实发生改变。然而，NAFLD发病机制中循环脂质的详细情况仍不清楚。
因此，本研究的目的是检测经肝活检证实的单纯性脂肪变性（SS）、非酒精性脂肪性肝炎（NASH）患者以及健康受试者的循环脂质，并探讨与肝脏基因表达相关的潜在机制。
测定了31名健康活体肝供者（作为健康对照，HC）、26例单纯性肝脂肪变性患者（SS）和20例进展期NASH患者的血浆磷脂和脂肪酸组成。通过Illumina微阵列分析了22例HC、16例SS和14例NASH患者的肝脏基因表达。
相对于疾病进展，磷脂酰乙醇胺（PE）浓度升高，HC＜SS＜NASH（170＜210＜250μg/ml），HC与NASH之间有显著差异（P＜0.05）。与HC相比，SS和NASH患者的循环磷脂酰丝氨酸（PS）和磷脂酰肌醇水平更高（P＜0.05），但SS与NASH之间无差异。磷脂的脂肪酸组成也发生了重塑。特别是，SS和NASH患者PS中的二十二碳六烯酸和花生四烯酸相对于HC更高（P＜0.05）。差异表达的肝脏基因包括分别参与PE合成和PS转运的ETNK1和PLSCR1。
本研究表明，磷脂代谢存在紊乱，这种紊乱在SS中存在，但在NASH中更明显。针对脂质代谢的干预研究可能对SS和NASH有益。
